FP-1039 is a ligand trap that is designed to selectively intervene in fibroblast growth factor (FGF) signaling. FGFs are a family of 22 related extracellular proteins called ligands that normally regulate cell proliferation and survival in humans. They act by binding to and activating FGF receptors (FGFRs), which are cell surface proteins that transmit growth signals to cells. Certain FGFs promote growth of multiple solid tumors by binding and activating FGFRs.

In certain tumor types there is amplification of the FGFR1 gene, which results in over-expression of the FGFR1 protein on the surface of the tumor cell. Also, tumors sometimes overexpress fibroblast growth factor ligands for FGFR1, such as FGF2.  Approximately half of the 22 known FGFs can activate FGFR1, leading to increased FGF signaling and cancerous cell growth. Another function of FGF proteins and their receptors is to mediate the growth of blood vessel tissue. This process, known as angiogenesis, can accelerate the growth of tumors by increasing the supply of oxygen and other nutrients available to the cancer cells.


As a ligand trap, FP-1039 is thought to bind to FGF ligands circulating in the extracellular space, thereby preventing these signaling proteins from reaching FGFR1 on the surface of tumor cells where they would otherwise stimulate cancer cell division and/or angiogenesis. However, FP-1039 is not believed to bind to certain "hormonal" FGFs, including FGF23, which regulates phosphate levels in the blood. As a result, treatment with FP-1039 has not been shown to cause hyperphosphatemia, a side effect seen with small molecule inhibitors of FGF receptors, which block the activity of both cancer-associated FGFs and FGF23.

FP-1039 Trial

Five Prime successfully completed a Phase 1 clinical trial of FP-1039 in 39 patients with solid tumors and licensed the development and commercialization rights for FP-1039 in the U.S., Europe and Canada to GlaxoSmithKline (GSK).

GSK is conducting and funding a Phase 1b trial of FP-1039 that is designed as a multicenter, non-randomized, parallel-group, uncontrolled, open-label trial. This clinical trial will enroll up to 30 mesothelioma patients at the expansion dose of 15 mg/kg. The trial was designed to evaluate the safety, tolerability, dosage, response rate and duration of response of FP-1039 in combination with front-line pemetrexed and cisplatin in mesothelioma, a tumor in which the FGF-2 ligand is overexpressed.

GSK presented preliminary clinical safety and efficacy data from the Phase 1b trial at the World Conference on Lung Cancer on September 9, 2015. 

FP-1039 Status

On March 9, 2016, GSK notified Five Prime that they will return their FP-1039 rights to Five Prime and the license agreement will terminate on September 5, 2016.

After the termination of the license agreement, Five Prime will again hold worldwide rights for FP-1039. Five Prime will continue to obtain clinical data to make decisions on the future development of FP-1039 in mesothelioma based on the maintenance and durability of patient responses as the Phase 1b trial progresses and the data mature.

Mesothelioma is a disease with high unmet medical need and high mortality rate. A majority of mesothelioma patients have tumors with abnormally high levels of FGF-2. In preclinical testing, we observed inhibition of mesothelioma tumor growth with single-agent FP-1039. Mesothelioma is an orphan indication in the United States with a prevalence of about 4,000 patients and incidence of about 3,000 patients. Worldwide, there are a total of approximately 14,000 cases of mesothelioma diagnosed each year.